Variant 5-74715459-CTT-CT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000521.4(HEXB):c.902-48delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,267,100 control chromosomes in the GnomAD database, including 9,255 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1682 hom., cov: 30)

Exomes 𝑓: 0.11 ( 7573 hom. )

Consequence

HEXB
NM_000521.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.22

Variant links:

Genes affected

HEXB (HGNC:4879): (hexosaminidase subunit beta) Hexosaminidase B is the beta subunit of the lysosomal enzyme beta-hexosaminidase that, together with the cofactor GM2 activator protein, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines. Beta-hexosaminidase is composed of two subunits, alpha and beta, which are encoded by separate genes. Both beta-hexosaminidase alpha and beta subunits are members of family 20 of glycosyl hydrolases. Mutations in the alpha or beta subunit genes lead to an accumulation of GM2 ganglioside in neurons and neurodegenerative disorders termed the GM2 gangliosidoses. Beta subunit gene mutations lead to Sandhoff disease (GM2-gangliosidosis type II). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

HEXB links:

HEXB (HGNC:):

HEXB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 5-74715459-CT-C is Benign according to our data. Variant chr5-74715459-CT-C is described in ClinVar as [Benign]. Clinvar id is 256361.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEXB	NM_000521.4 linkuse as main transcript	c.902-48delT		intron_variant		ENST00000261416.12	NP_000512.2	P07686A0A024RAJ6
HEXB	NM_001292004.2 linkuse as main transcript	c.227-48delT		intron_variant			NP_001278933.1	P07686Q5URX0

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
HEXB	ENST00000261416.12 linkuse as main transcript	c.902-48delT	intron_variant	1	NM_000521.4	ENSP00000261416.7	P07686
HEXB	ENST00000511181.5 linkuse as main transcript	c.227-48delT	intron_variant	1		ENSP00000426285.1	Q5URX0
HEXB	ENST00000504459.5 linkuse as main transcript	n.99-48delT	intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20578

AN:

151954

Hom.:

1680

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.203

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.172

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.0499

Gnomad MID

AF:

0.150

Gnomad NFE

AF:

0.0990

Gnomad OTH

AF:

0.147

GnomAD3 exomes

AF:

0.131

AC:

31367

AN:

239656

Hom.:

2485

AF XY:

0.125

AC XY:

16188

AN XY:

129914

show subpopulations

Gnomad AFR exome

AF:

0.195

Gnomad AMR exome

AF:

0.255

Gnomad ASJ exome

AF:

0.115

Gnomad EAS exome

AF:

0.173

Gnomad SAS exome

AF:

0.124

Gnomad FIN exome

AF:

0.0523

Gnomad NFE exome

AF:

0.0969

Gnomad OTH exome

AF:

0.120

GnomAD4 exome

AF:

0.110

AC:

122759

AN:

1115028

Hom.:

7573

Cov.:

AF XY:

0.109

AC XY:

62408

AN XY:

571096

show subpopulations

Gnomad4 AFR exome

AF:

0.199

Gnomad4 AMR exome

AF:

0.249

Gnomad4 ASJ exome

AF:

0.113

Gnomad4 EAS exome

AF:

0.152

Gnomad4 SAS exome

AF:

0.121

Gnomad4 FIN exome

AF:

0.0529

Gnomad4 NFE exome

AF:

0.0995

Gnomad4 OTH exome

AF:

0.122

GnomAD4 genome

AF:

0.136

AC:

20618

AN:

152072

Hom.:

1682

Cov.:

AF XY:

0.134

AC XY:

9994

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.192

Gnomad4 AMR

AF:

0.204

Gnomad4 ASJ

AF:

0.107

Gnomad4 EAS

AF:

0.172

Gnomad4 SAS

AF:

0.133

Gnomad4 FIN

AF:

0.0499

Gnomad4 NFE

AF:

0.0990

Gnomad4 OTH

AF:

0.146

Alfa

AF:

0.118

Hom.:

211

Bravo

AF:

0.152

Asia WGS

AF:

0.175

AC:

609

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 21, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 27, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over